Recent advances revealed that classical class I MHC molecules (class Ia), crucial for cell-mediated immunity against pathogens, represent only a small subset of the family of related proteins displaying potential for antigen presentation. The candidate genes for nonclassical class I MHC molecules (class Ib) were identified in all vertebrates including rodents and man. In a few cases class Ib-binding peptides were characterized and their structural features were used to deduce the physiological roles of the presenting molecules. Thanks to this approach, it is now known that murine H-2M3 class Ib molecules participate in the immune response against intracellular pathogen, Listeria monocytogenes. The antigen presentation functions of other class Ib proteins have not been yet defined. We propose to examine the structural properties of self-peptides associated with five different murine class Ib molecules. The specific aims are: 1) to perform a systematic analysis of anchor residues required for binding to Q7 antigen, identify proteins that carry the Q7 binding motif, synthesize the candidate peptide epitopes from known pathogens and test for binding to Q7 2) to overexpress Q6, Q1O, Qa-1 and H-2M3 class Ib complexes in tissue cultured cells and characterize peptides associated with these molecules, using the strategies employed previously by us and our collaborators to define SQ7-bound self-peptides. The results of these studies will provide insights into the biological significance of antigen presentation by class Ib molecules and will generate information relevant to the understand in of their roles in immune response against pathogens and tumors as well as their participation in transplant rejection and in autoimmune reactions.